Complex regulation of gene expression is fundamental for the development and function of the human brain. Expression of genes is regulated by both RNA splicing and RNA modifications, with N6-methyladenosine (m6A) being the most abundant RNA modification. The brain exhibits the highest levels of RNA splicing and m6A modification in human tissues, but many of their functional roles and interactions remain to be discovered. Nanopore long-read direct RNA sequencing (DRS) can detect both RNA modifications and quantify isoform expression, allowing for simultaneous investigation into transcriptomics and epitranscriptomics to explore how these different regulators of gene expression contribute to brain function. We applied DRS to three post-mortem human brain regions: prefrontal cortex, caudate and cerebellum. Our results show thousands of differentially expressed isoforms, 1,270 isoforms with changes in polyA tail lengths and 2,401 isoforms with differential m6A modification levels across brain regions. There was little overlap between differentially modified and differentially expressed isoforms, which suggests distinct roles for RNA modification and expression as regulatory mechanisms. The cerebellum showed the highest global levels of m6A modification and highly modified genes in this region were associated with RNA metabolism. In prefrontal cortex and caudate, highly modified genes were strongly associated with synaptic activity, posing differing roles for m6A between brain regions. The most heavily modified gene in brain was the lncRNA TUG1, which is a target for various cancer therapies. We find more than 100 m6A sites within the TUG1 gene. We also find a large overlap between highly modified genes and neuropsychiatric risk genes. Our findings reveal new insights into brain region specificity and function, providing avenues for investigation into brain development and neurological disorders.